Antimicrobial compounds, compositions and methods of use thereof
Described herein are antimicrobial compounds identified via a high-throughput screen to identify compounds that produce anucleate cells in E. coli after cell division occurs. Compound 1 (5-nonyloxytryptamine) and its analogs are small molecule inhibitors of the nucleoid occlusion system and/or proteins that are responsible for maintaining the structure of the chromosome. The antimicrobial compounds are useful to treat bacterial infections as well as to inhibit bacterial growth.
1. An antimicrobial compound of formula 10,
2. A pharmaceutical composition comprising the antimicrobial compound of claim 1 and a pharmaceutically acceptable excipient.
3. The pharmaceutical formulation of claim 2 , in the form of a composition for topical administration.
4. The pharmaceutical formulation of claim 2 , in the form of a composition for systemic administration.
5. A method of treating a subject in need of treatment for a bacterial infection comprising administering to the subject a compound of Formula II, or a pharmaceutically acceptable salt thereof,
wherein
R is a substituted or unsubstituted C 5 -C 18 alkyl group, a substituted or unsubstituted C 5 -C 18 alkenyl group, a substituted or unsubstituted C 5 -C 18 alkynyl group, a substituted or unsubstituted C 5 -C 18 cycloalkyl group, a substituted or unsubstituted C 6 -C 18 cycloalkenyl group, a substituted or unsubstituted C 8 -C 18 cycloalkynyl group, a substituted or unsubstituted C 5 -C 18 heteroalkyl group, a substituted or unsubstituted C 5 -C 18 heterocycloalkyl group, a substituted or unsubstituted C 7 -C 30 arylalkyl group, a substituted or unsubstituted C 7 -C 30 aryloxyalkyl group, or a substituted or unsubstituted C 7 -C 30 arylthioalkyl group.
6. The method of claim 5 , wherein, R is a substituted or unsubstituted C 5 -C 18 alkyl group, a substituted or unsubstituted C 5 -C 18 alkenyl group, or a substituted or unsubstituted C 5 -C 18 alkynyl group.
7. The method of claim 6 , wherein R is a substituted or unsubstituted C 5 -C 18 alkyl group.
8. The method of claim 7 , wherein R is substituted with one or more C 1 -C 20 alkyl groups, C 6 -C 20 aryl, and/or C 7 -C 13 arylalkyl groups.
9. The method of claim 7 , wherein R is substituted with one or more C 1 -C 4 alkyl groups or a C 6 -C 10 aryl group.
10. The method of claim 5 , wherein the compound of Formula II is
11. The method of claim 5 , wherein the bacteria causing the infection are Gram-negative bacteria, Gram-positive bacteria, or bacteria that are neither Gram-positive nor Gram-negative.
12. The method of claim 11 , wherein the Gram-negative bacteria is Escherichia coli, Pseudomonas aeruginosa, Candidatus liberibacter, Agrobacterium tumefaciens, Branhamella catarrhalis, Citrobacter diversus, Enterobacter aerogenes, Klebsiella pneumoniae, Proteus mirabilis, Salmonella typhimurium, Neisseria meningitidis, Serratia marcescens, Shigella sonnei, Shigella boydii, Neisseria gonorrhoeae, Acinetobacter baumannii, Salmonella enteriditis, Fusobacterium nucleatum, Veillonella parvula, Bacteroides forsythus, Actinobacillus actinomycetemcomitans, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Helicobacter pylori, Francisella tularensis, Yersinia pestis, Vibrio cholera, Shigella boydii, Morganella morganii, Edwardsiella tarda, Campylobacter jejuni , or Haemophilus influenzae.
13. The method of claim 11 , wherein the Gram-positive bacteria is a species of Bacillus, Listeria, Staphylococcus, Streptococcus, Enterococcus, Corynebacterium, Propionibacterium or Clostridium.
14. The method of claim 13 , wherein the Gram-positive bacteria is Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, Enterococcus faecalis, Streptococcus pyogenes, Bacillus cereus , or Bacillus anthracis.
15. The method of claim 11 , wherein the bacteria are carbapenam-resistant bacteria, methicillin-resistant Staphylococcus aureus , vanccomycin-resistant Enterococci or multi-drug resistant Neisseria gonorrhoeae.
16. The method of claim 5 , wherein the subject is a mammal.
17. The method of claim 16 , wherein the mammal is a human.
18. The method of claim 5 , wherein administration is topical administration.
19. The method of claim 5 , wherein administration is systemic administration.
20. A method of inhibiting bacterial growth comprising contacting bacteria with an effective amount of the antimicrobial compound of Formula II or a pharmaceutically acceptable salt thereof,
wherein
R is a substituted or unsubstituted C 5 -C 18 alkyl group, a substituted or unsubstituted C 5 -C 18 alkenyl group, a substituted or unsubstituted C 5 -C 18 alkynyl group, a substituted or unsubstituted C 5 -C 18 cycloalkyl group, a substituted or unsubstituted C 6 -C 18 cycloalkenyl group, a substituted or unsubstituted C 8 -C 18 cycloalkynyl group, a substituted or unsubstituted C 5 -C 18 heteroalkyl group, a substituted or unsubstituted C 5 -C 18 heterocycloalkyl group, a substituted or unsubstituted C 7 -C 30 arylalkyl group, a substituted or unsubstituted C 7 -C 30 aryloxyalkyl group, or a substituted or unsubstituted C 7 -C 30 arylthioalkyl group.
21. The method of claim 20 , wherein, R is a substituted or unsubstituted C 5 -C 18 alkyl group, a substituted or unsubstituted C 5 -C 18 alkenyl group, or a substituted or unsubstituted C 5 -C 18 alkynyl group.
22. The method of claim 21 , wherein R is a substituted or unsubstituted C 5 -C 18 alkyl group.
23. The method of claim 20 , wherein R is substituted with one or more C 1 -C 20 alkyl groups, C 6 -C 20 aryl, and/or C 7 -C 13 arylalkyl groups.
24. The method of claim 20 , wherein R is substituted with one or more C 1 -C 4 alkyl groups or a C 6 -C 10 aryl group.
25. The method of claim 20 , wherein the compound of Formula II is
26. The method of claim 20 , wherein the bacteria are actively growing or are in the stationary phase.
27. The method of claim 20 , wherein the bacteria are in the form of a biofilm.